RESUMEN

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.

Asunto(s)

Microtia Congénita , Remoción del Cabello , Procedimientos de Cirugía Plástica , Humanos , Femenino , Masculino , Estudios Retrospectivos , Microtia Congénita/cirugía , Remoción del Cabello/métodos , Procedimientos de Cirugía Plástica/métodos , Adolescente , Adulto Joven , Adulto , Niño , Terapia por Láser/métodos , Terapia por Láser/instrumentación

RESUMEN

This report details the genome sequence of Escherichia coli strain Hakim RU_GHWS, isolated from sewage water. The assembled genome comprises 5.022 Mb with 77.675× coverage, depicting an average GC content of 50.50%. This genome contains 10 CRISPR arrays, 14 prophages, 65 antibiotic resistance genes, and 28 virulence factor genes.

RESUMEN

Drug-resistant Mycobacterium tuberculosis is a significant cause of infectious disease morbidity and mortality for which new antimicrobials are urgently needed. Inhibitors of mycobacterial respiratory energy metabolism have emerged as promising next-generation antimicrobials, but a number of targets remain unexplored. Succinate dehydrogenase (SDH), a focal point in mycobacterial central carbon metabolism and respiratory energy production, is required for growth and survival in M. tuberculosis under a number of conditions, highlighting the potential of inhibitors targeting mycobacterial SDH enzymes. To advance SDH as a novel drug target in M. tuberculosis, we utilized a combination of biochemical screening and in-silico deep learning technologies to identify multiple chemical scaffolds capable of inhibiting mycobacterial SDH activity. Antimicrobial susceptibility assays show that lead inhibitors are bacteriostatic agents with activity against wild-type and drug-resistant strains of M. tuberculosis. Mode of action studies on lead compounds demonstrate that the specific inhibition of SDH activity dysregulates mycobacterial metabolism and respiration and results in the secretion of intracellular succinate. Interaction assays demonstrate that the chemical inhibition of SDH activity potentiates the activity of other bioenergetic inhibitors and prevents the emergence of resistance to a variety of drugs. Overall, this study shows that SDH inhibitors are promising next-generation antimicrobials against M. tuberculosis.

RESUMEN

The service life of the lithium-oxygen (Li-O2) battery is an essential factor in measuring the performance of the battery, and it is also imperative to clarify the reason for battery termination. In this work, the positive electrode of a nonaqueous Li-O2 battery was selected after cutoff under different discharge conditions, and the digital reconstruction model of the positive electrode was carried out by X-CT technology. The reconstructed positive electrode's structural characteristics, material transport characteristics, and electrical conductivity were analyzed. It is found that the positive electrode has an apparent expansion phenomenon after constant capacity cyclic charge and discharge, but this situation is not evident after deep discharge. After the constant capacity test is cut off, the product distribution range in the positive electrode is more comprehensive and the material transport efficiency is higher. However, after deep discharge, the product distribution in the positive electrode is more concentrated and the material transport efficiency is lower. There are apparent differences in the termination mechanism between constant capacity cycle discharge and deep discharge. This paper provides a compelling theoretical basis for revealing the discharge termination mechanism of nonaqueous Li-O2 batteries.

Asunto(s)

Anastomosis Quirúrgica , Endosonografía , Humanos , Masculino , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Constricción Patológica/cirugía , Constricción Patológica/etiología , Endosonografía/métodos , Estenosis Esofágica/cirugía , Estenosis Esofágica/etiología , Esófago/cirugía , Esófago/diagnóstico por imagen , Yeyunostomía/métodos , Yeyuno/cirugía , Ultrasonografía Intervencional

RESUMEN

In this study, a series of novel thieno [3, 2-b]pyridinone derivatives were designed and synthesized using a scaffold hopping strategy. Six compounds showed potent anti-mycobacterial activity (minimum inhibitory concentration (MIC) ≤ 1 µg/mL) against Mycobacterium tuberculosis (Mtb) UAlRa. Compound 6c displayed good activity against Mtb UAlRv (MIC = 0.5-1 µg/mL). Compounds 6c and 6i also showed activity against Mtb UAlRa in macrophages and exhibited low cytotoxicity against LO-2 cells. The selected compounds displayed a narrow antibacterial spectrum, with no activity against representative Gram-positive, Gram-negative bacteria, as well as fungi. Furthermore, compound 6c demonstrated favorable oral pharmacokinetic properties with a T1/2 value of 47.99 h and exhibited good in vivo activity in an acute mouse model of tuberculosis (TB). The target of compound 6c was identified as a NADH-dependent enoyl-acyl carrier protein reductase (InhA) by genome sequencing of spontaneously compound 6c-resistant Mtb mutants, indicating that compound 6c may not require activation and can directly target InhA. In vitro antimicrobial assays against a recombinant M. smegmatis overexpressing the Mtb-InhA, along with InhA inhibition assays, confirmed that InhA is the target of thieno [3, 2-b]pyridinone derivatives. Overall, this study identified thieno [3, 2-b]pyridinone scaffold as a novel chemotype that is promising for the development of anti-TB agents.

RESUMEN

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent antimycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further antimycobacterial drug or regimen optimization, especially in the case of nonreplicating mycobacteria.

RESUMEN

In the field of oral and maxillofacial surgery, extensive oral soft-tissue injuries occur repeatedly in clinical practice; however, effective restorative materials are lacking. In this study, a biodegradable waterborne polyurethane patch featuring a mucosa bionic bilayer structure is presented. This patch consists of a porous scaffold layer that faces the lesion, incorporating a polydopamine coating to achieve sustained release of epidermal growth factors (EGFs) for mucosal defect reconstruction. Additionally, there is a dense barrier layer toward the oral cavity loaded with silver nanoparticles, which prevents bacteria from entering the wound and simultaneously acts as a physical barrier. This patch can sustainably release EGF in vitro for 2 weeks, thereby facilitating the proliferation and migration of HaCaT and L929 cells, while effectively killing common oral cavity bacteria. In a rabbit buccal mucosal full-thickness defect model, the patch demonstrates better efficacy than the clinical benchmark, decellularized extracellular matrix (dECM). It effectively reduces wound inflammation and significantly upregulates gene expression associated with epithelialization by activating the EGF/epidermal growth factor receptor (EGFR) pathway. These mechanisms promote the proliferation, differentiation, and migration of epithelial/keratinocyte cells, ultimately expediting mucosal defect healing and wound closure.

Asunto(s)

Factor de Crecimiento Epidérmico , Mucosa Bucal , Poliuretanos , Plata , Poliuretanos/química , Poliuretanos/farmacología , Animales , Conejos , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/metabolismo , Humanos , Factor de Crecimiento Epidérmico/química , Factor de Crecimiento Epidérmico/farmacología , Factor de Crecimiento Epidérmico/metabolismo , Plata/química , Plata/farmacología , Ratones , Repitelización/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Nanopartículas del Metal/química , Línea Celular , Antibacterianos/farmacología , Antibacterianos/química , Movimiento Celular/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Receptores ErbB/metabolismo , Polímeros/química , Polímeros/farmacología , Células HaCaT , Indoles

RESUMEN

The escalating prevalence of obesity poses significant health challenges due to its direct association with various diseases. Most existing medications, such as appetite suppressants and fat absorption inhibitors, suffer from limited effectiveness and undesirable side effects. Here, inspired by the versatile metabolic effects of turmeric, we developed a naturally derived nanoformulation of "Reconstructed Turmeric-derived Nanovesicles (Rec-tNVs)" for obesity treatment. Employing quantitative nanoflow cytometry, a four-orders-of-magnitude increase in curcumin content (∼108 molecules per particle) was identified in individual Rec-tNVs compared to their ultracentrifugation-isolated counterparts. Rec-tNVs, featuring highly aggregated curcumin arrangements and other coencapsulated bioactive compounds, demonstrated a dose-dependent lipid-lowering effect in mature 3T3-L1 cells by promoting lipolysis, suppressing lipogenesis, inducing adipocyte browning, and triggering apoptosis after internalization via multiple pathways. In vivo experiments revealed that Rec-tNVs alleviated obesity more effectively than free curcumin and achieved weight reductions of 18.68 and 14.56% through intragastric and subcutaneous delivery, respectively, in high-fat-diet mouse models over a four-week treatment period. These effects were attributed to targeted actions on adipose tissues and systemic impacts on metabolism and gut microbiota composition. Overall, this study underscores the multifaceted antiobesity efficacy of Rec-tNVs, and offers a promising paradigm for developing plant-derived nanovesicle-based therapeutics.

Asunto(s)

Células 3T3-L1 , Curcuma , Curcumina , Obesidad , Animales , Ratones , Curcuma/química , Obesidad/tratamiento farmacológico , Curcumina/farmacología , Curcumina/química , Ratones Endogámicos C57BL , Masculino , Dieta Alta en Grasa , Apoptosis/efectos de los fármacos , Nanopartículas/química

RESUMEN

Lard is highly appreciated for its flavor. However, it has not been elucidated how to consume lard while at the same time eliminating its adverse effects on postpartum cognitive function. Female mice were divided into three groups (n = 10): soybean oil (SO), lard oil (LO), and a mixture of soybean oil and lard at a ratio of 1:1 (LS). No significant difference was observed between the SO and LS groups in behavioral testing of the maternal mice, but the LO group was significantly worse compared with these two groups. Moreover, the SO and LS supplementation increased docosahexaenoic acid (DHA) and total n-3 polyunsaturated fatty acid (PUFA) levels in the brain and short-chain fatty acid (SCFA)-producing bacteria in feces, thereby mitigating neuroinflammation and lowering the p-ERK(1/2)/ERK(1/2), p-CREB/CREB, and BDNF levels in the brain compared to the LO group. Collectively, the LS group inhibited postpartum cognitive impairment by regulating the brain fatty acid composition, neuroinflammation, gut microbiota, and the SCFA/ERK(1/2)/CREB/BDNF signaling pathway compared to lard.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Encéfalo , Disfunción Cognitiva , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Ácidos Grasos Volátiles , Periodo Posparto , Aceite de Soja , Animales , Femenino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratones , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Aceite de Soja/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos Grasos/metabolismo , Transducción de Señal/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos

RESUMEN

Host-microbe interactions are virtually bidirectional, but how the host affects their microbiome is poorly understood. Here, we report that the host is a critical modulator to regulate the lifestyle switch and pathogenicity heterogeneity of the opportunistic pathogens Serratia marcescens utilizing the Drosophila and bacterium model system. First, we find that Drosophila larvae efficiently outcompete S. marcescens and typically drive a bacterial switch from pathogenicity to commensalism toward the fly. Furthermore, Drosophila larvae reshape the transcriptomic and metabolic profiles of S. marcescens characterized by a lifestyle switch. More importantly, the host alters pathogenicity and heterogeneity of S. marcescens in the single-cell resolution. Finally, we find that larvae-derived AMPs are required to recapitulate the response of S. marcescens to larvae. Altogether, our findings provide an insight into the pivotal roles of the host in harnessing the life history and heterogeneity of symbiotic bacterial cells, advancing knowledge of the reciprocal relationships between the host and pathogen.

Asunto(s)

Drosophila melanogaster , Interacciones Huésped-Patógeno , Larva , Serratia marcescens , Animales , Serratia marcescens/patogenicidad , Serratia marcescens/genética , Serratia marcescens/fisiología , Larva/microbiología , Drosophila melanogaster/microbiología , Análisis de la Célula Individual , Simbiosis , Drosophila/microbiología , Virulencia/genética

RESUMEN

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. METHODS: This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. FINDINGS: The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 µm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. INTERPRETATION: Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.

Asunto(s)

Inhibidores de la Angiogénesis , Biomarcadores , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/diagnóstico por imagen , Resultado del Tratamiento , Nomogramas , Pólipos/tratamiento farmacológico , Pólipos/diagnóstico por imagen , Pólipos/diagnóstico , Angiografía con Fluoresceína/métodos , Enfermedades de la Coroides/tratamiento farmacológico , Enfermedades de la Coroides/diagnóstico por imagen , Enfermedades de la Coroides/diagnóstico , Vasculopatía Coroidea Polipoidea

RESUMEN

Dry fractionation represents a significant technique for separation of diverse fractions from beef tallow. The objective of this study was to undertake a systematic investigation of alterations in physicochemical properties, crystallization behavior, thermal properties, and flavor compounds that occur during the beef tallow dry fractionation process. The solid component yielded at 40, 30, and 15 °C were 44.88%, 33.72%, and 13.04% respectively, with an 8.36% liquid content at 15 °C, which was consistent with the characteristics of saturated fatty acids content. The ß - ß' transformation in the dry fractionation process was clearly revealed by X-ray diffraction. Differential scanning calorimetry curves exhibited alterations in exothermic and endothermic peak, as well as enthalpy. Electronic nose identified short-chain compounds, aldehydes, ketones, and nitrogen-containing substances as flavor compounds. Volatile compounds were quantified using HS-SPME-GC-MS. Overall, dry fractionation produces beef tallow fractionated compounds with diverse physicochemical properties and aromatic-active substances, thereby expanding its potential utilization.

Asunto(s)

Aromatizantes , Bovinos , Animales , Aromatizantes/química , Aromatizantes/aislamiento & purificación , Grasas/química , Fraccionamiento Químico/métodos , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Rastreo Diferencial de Calorimetría , Gusto , Difracción de Rayos X

RESUMEN

Oligodendrocyte precursor cells (OPCs) migrate extensively using blood vessels as physical scaffolds in the developing central nervous system. Although the association of OPCs with the vasculature is critical for migration, the regulatory mechanisms important for OPCs proliferative and oligodendrocyte development are unknown. Here, a correlation is demonstrated between the developing vasculature and OPCs response during brain development. Deletion of endothelial stimulator of interferon genes (STING) disrupts angiogenesis by inhibiting farnesyl-diphosphate farnesyltransferase 1 (FDFT1) and thereby reducing cholesterol synthesis. Furthermore, the perturbation of metabolic homeostasis in endothelial cells increases interleukin 17D production which mediates the signal transduction from endothelial cells to OPCs, which inhibits oligodendrocyte development and myelination and causes behavioral abnormalities in adult mice. Overall, these findings indicate how the endothelial STING maintains metabolic homeostasis and contributes to oligodendrocyte precursor cells response in the developing neocortex.

RESUMEN

Direct methane conversion to high-value chemicals under mild conditions is attractive yet challenging due to the inertness of methane and the high reactivity of valuable products. This work presents an efficient and selective strategy to achieve direct methane conversion through the oxidative coupling of methane over a visible-responsive Au-loaded CeO2 by photon-phonon co-driven catalysis. A record-high ethane yield of 755 µmol h-1 (15,100 µmol g-1 h-1) and selectivity of 93% are achieved under optimised reaction conditions, corresponding to an apparent quantum efficiency of 12% at 365 nm. Moreover, the high activity of the photocatalyst can be maintained for at least 120 h without noticeable decay. The pre-treatment of the catalyst at relatively high temperatures introduces oxygen vacancies, which improves oxygen adsorption and activation. Furthermore, Au, serving as a hole acceptor, facilitates charge separation, inhibits overoxidation and promotes the C-C coupling reaction. All these enhance photon efficiency and product yield.

RESUMEN

BACKGROUND: Suicide is influenced by multiple factors. However, the mechanisms through which these factors influence suicide remain understudied. This study aims to examine the relationship between parenting styles (warmth, control, indulgence, humiliation, and neglect), coping, self-esteem, depression, and suicidality (suicidal ideation and suicide attempts) among college students. METHODS: Cross-sectional data were collected from 2369 undergraduates (mean age = 20.10 years) including 1201 women (50.7%) at four Chinese colleges. RESULTS: Students reported high rates of suicidal behaviors (12.7% suicidal ideation, 6.4% suicidal attempts) and depression (37%). Structural equation modeling indicated that warmth (+) had associations with coping. Coping was linked to self-esteem and depression. Depression (+), self-esteem (-), warmth (-), and neglect (+) had direct correlations with suicidality. Self-esteem mediated the relationships between warmth and depression. CONCLUSIONS: Future prevention intervention efforts aimed at reducing depression and suicidal behaviors should prioritize the promotion of positive parenting styles and the avoidance of negative ones. College mental health services should emphasize positive and optimistic coping strategies to enhance students' self-esteem.

RESUMEN

OBJECTIVE: Perimenopause is the period from the early menopausal transition to 12 months after the final menstrual period. The clustering of menopausal symptoms poses a challenge for perimenopausal management. Core symptoms are targets for interventions that can alleviate other related symptoms. Bridge symptoms are connectors that link related symptom clusters and can improve the effectiveness of interventions. This study aims to construct a network structure of menopausal symptoms and to identify core and bridge symptoms as a reference for future management. METHODS: Two hundred forty-two Chinese perimenopausal women were included in the survey. The structure and associations of the menopausal symptoms assessed by the Greene Climacteric Scale were analyzed using a network analysis. We generated the network structure graph using R software and checked its accuracy and stability. RESULTS: In the menopausal transition, the most prevalent symptoms were feeling tired or lacking in energy, excitability, and irritability. Sexual dysfunction was common among early postmenopausal women. Irritability (S = 7.16, C = 0.0167, B = 8) was a core symptom of the network. The depressive symptom cluster was a core symptom cluster, most of which have high centrality indices. Excitability (B = 6) was a bridge symptom connecting the anxiety and depressive symptom clusters. CONCLUSIONS: Our study has highlighted the crucial significance of irritability and excitability in perimenopausal management. Overcoming the challenges of perimenopausal management requires the public to ameliorate the prejudice and stigma associated with emotional symptoms.

RESUMEN

The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus. IMPORTANCE: This study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.

RESUMEN

Cathelicidins, a major class of antimicrobial peptides (AMPs), hold considerable potential for antimicrobial drug development. In the present study, we identified a novel cathelicidin AMP (TC-33) derived from the Chinese tree shrew. Despite TC-33 demonstrating weak antimicrobial activity, the novel peptide TC-14, developed based on its active region, exhibited a 432-fold increase in antimicrobial activity over the parent peptide. Structural analysis revealed that TC-14 adopted an amphipathic α-helical conformation. The bactericidal mechanism of TC-14 involved targeting and disrupting the bacterial membrane, leading to rapid membrane permeabilization and rupture. Furthermore, TC-14 exhibited a high-safety profile, as evidenced by the absence of cytotoxic and hemolytic activities, as well as high biocompatibility and safety in vivo. Of note, its potent antimicrobial activity provided significant protection in a murine model of skin infection. Overall, this study presents TC-14 as a promising drug candidate for antimicrobial drug development.

RESUMEN

AIMS: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes. METHODS: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality. RESULTS: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57]). CONCLUSION: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment.